Phosphonic acid derivatives



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Patented Dec. 8, 1959 It has to be understood; however,,that these equations are given byway of illustration only and that other phosphonicanditliioph'osphonic' acid halides as well as PHOSPHONIC ACID'DERIVATIVES ErnsLSchegk, WuPPeltaLElberfeld, and Gerhard Schra- 5 according to the present invention dbl; 'Wuppertal Cmnenherg, Germany, assignors to Farbenfa'briken: Bayer Aktiengesellschaft, Leverkusen,

Other examples" of phosphonicor thiophosphonic acid ester halides are: ethyl phosphonic acid ethyl. ester chloride, propyl phos- Gemauyi'a'corp'omhon of'Germany phonic acid ethyl ester chloride, phenyl phosphonic acid No Drawing, Application August .14, 1-957 ethyl ester chloride, p-chlorophenyl phosphonic acid ethyl 678,031 ester chloride, 3,4-dichloroph'enyl'phosphonic acid ethyl L v y ester. chloride, and the like. Also the corresponding, claims'pnomy apphcatwncermany August 1956 thiophosphonic acid derivatives as well as other alkyl 4 Claims. (Cl. 260-461) esters such as the methyl; propyl,,butyl esters and'the like may be used in the same way. 1

Other substituted phenols, which may be used according to the present invention are: 0-, mor p-phenyl mercapto phenol, o-, mor p-propyl mercapto phenol, 0-, mor p-phenyl mercapto phenol, Z-methylmercapto-p-cresol, 3-methyl mercapto-p-cresol, 2'-ethyl mercapto-p-cresol, 3-ethyl mercapto-p-cresol, other alkyl mercapto-oand" m-cresols, Z-ethyl' mercapto-p-chlorophenol, Z-methyl mercapto-p-chlorophenol, Z-phenyl mercapto-p-chloroin which R and R1 Stand f alkyl or aryl radicals, phenol, and the, like. 'The corresponding sulfoxides and stands for aryl radicals, R stands for lower alkyl radicals, sulfoms the above 531d mercaptanes as Well as especially containing 1 to 4 carbon atoms, X stands for 25 Of Other simllarv mercaptanes may also be used according oxyggjlo t lf d n Stands f 0 or a whole number to the present invention. But in case the sulfoxides or f i 2, sulfonesshouldv be prepared it is also possible to oxidize Some phosphonic and thiophosphonic acid esters are the intermediate mercaptophenyl phosphonic acid esters valuable insecticides, and the present invention relates to to these sulfoxides and sulfones. This may be seen froma new class of these compounds, which shows good rethe following equation:

- O S OH O O S O( 0H3 2 CH3 sults -imeombating a plurality of insects, thus being also able to be used as plant protecting agents.

Generally the new compounds of the present invention salts of. the above said phenols or in the presence of acid may be obtained by reacting phosphonicor thiophosbinding agents. Suitable salts'of the phenols are especially phonic acid halides, especially chlorides With suitable 40 the alkali metal salts such as the sodium or potassium mercaptoisubstituted phenols. This reaction may be seen salt. If the reaction is carried out in the presence of acid from the following. equations: binding agents alkali. metal alcoholates, hydroxides or The: present invention relates'to and has as its objects 15 newphosphonic acid esters and their production. Gener-allythe new compounds of the present inventioncorrespend: to the following formula O CzHg The reaction generally should be carried out either with CHa-P S] OCaHb other substituted phenols may also eifectively be used carbonates are especially suitable to complete the inventive reaction.

The temperature range within which the reaction optionally takes place is between about to 100 C., but sometimes lower or higher temperatures may also be advisable. It is mostly advisable to start the reaction at lower temperatures or at room temperature and to complete it by heating on the steam bath.

For carrying out the inventive reaction the presence of inert solvents is advisable and acetone, lower alcohols such as methanol or ethanol, benzene, toluene, and the like are the most common solvents for this reaction.

The compounds of the present invention are generally valuable insecticides and plant protecting agents. They kill pests such as aphids, flies and mites and exhibit a very remarkable systemic action. A part of the inventive new phosphonic acid esters shows a remarkable activity against sucking insects such as caterpillars. The application of these compounds should be carried out according to the use of other known phosphor insecticides, i.e. in dilution or solution with solid or liquid carriers such as chalk, talk, bentonite, water, alcohols, liquid hydrocarbons etc. The inventive compounds may further be used in combination with other known insecticides or pesticides, etc. Effective concentrations of the compounds may vary also; generally, concentrations of 0.0001 to 1.0% kill pests effectively. The combinations of the compounds may be sprayed or dusted or otherwise brought in contact with pests or plants to be protected. They may also be used as aerosols.

The utility of the inventive compounds has been determined by using the phosphonic acid ester of the following formula against some common known insects and plant pests.

Solutions of this ester which have been prepared by using dimethyl formamide as auxiliary solvent (in the same amount as the active ingredient), and 50% by weight of the active ingredient of a commercial emulsifier consisting of benzyl hydroxy diphenyl polyglycol ether are used against Colorado beetles, black bean aphids, spider mites, and eggs of spider mites. With aqueous dilutions of the above shown mixture in a concentration of active ingredient of 0.01%-Colorado beetles are killed 100% 0.001%black bean aphids and spider mites are killed 0.0001%-eggs of spider mites are killed 100% The following examples are given by way of illustration only, without limiting the present invention thereto.

Example 1 other 2 hours at a temperature of 7075 0., then it is cooled down to room temperature and the sodium chloride is filtered off with suction. The filtrate is washed three times with 20 ml. of water and then dried oversodium sulfate. After filtration and distilling oflf of the solvent the raw ester is distilled in high vacuo. There are obtained 176 grams of a colorless, water-un'soluble oil (B.P. C.). Yield: 71.5% of the theoretical. Calc. for 246.3: P=l2.6%, S=13.0%. Found: P=11.6%, S=l3.9%.

DL on rats orally 1 mg./kg.

Example 2 47 grams of S-methyl thiohydrochinone sulfoxide (M.P. 107 C.) are suspended in 600 cc. of benzene. To this mixture there are added 57 grams of a sodium methylate solution containing 0.3 mol of sodium. The methanol is distilled ofi aceotropically with most of the benzene. The slurry so obtained is then dissolved in 250 ml. of methyl ethyl ketone. To this solution there are added while stirring and at a temperature of about 55-60 C. 50 grams of methyl phosphonic acid ethyl ester chloride. The solution is warmed for another hour at 70 C., then cooled down to room temperature and diluted with 300 ml. of ether. The reaction product is washed three times with 200 ml. of water. After drying over sodium sulfate the solvent is distilled oflf. The rcmaining colorless, Water-unsoluble oil is distilled in vacuo. There are obtained 32 grams of the new ester of the formula (B.P. 124 C.). Yield: 97% of the theoretical.

Calc. for 262.3: P=11.8%, S=12.2%, OC H 17.2% Found: P=10.3%, S=13.5%, OC H =16.7%.

DL on rats orally 1 mg./kg.

Example 3 61 grams of the sodium salt of S-methyl thiohydrochinone sulfone are dissolved in 300 ml. of methyl ethyl ketone. Then there are added while stirring and at a temperature of about 30 C. 55 grams of methyl phosphonic acid ethyl ester chloride. The temperature rises slowly to about 55 C. The reaction mixture is warmed for another hour at a temperature of 60 C. Then it is cooled down to room temperature and there are added 300 ml. of chloroform. The precipitated sodium chloride is filtered off with suction. The filtrate is Washed with 50 ml. of water three times. After drying over sodium sulfate the solvent is removed in vacuo. There are obtained 63 grams of the new ester of the formula Example 4 CH.: SCH:

To a suspension of 51 grams of the sodium salt (0.3 mol) of S-methyl thiopyrocatechol in 250 ml. of ethyl methyl ketone there are added at a temperature of about 30 C. 50 grams of methyl phosphonic acid ethyl ester chloride. After stirring for one hour at room temperature the temperature rises to 60 C. After cooling there are added 500 ml. of benzene and the reaction mixture is washed with water. The benzenic layer is dried over sodium sulfate and the solvent is distilled off in vacuo. The remaining colorless oil is distilled in high vacuo.

'le'ss" oil; Yield! 94% r the theoretical. I

Cale-z C 48.77%, H 6.l4% -'P :-1 2.60%, s 13.02%. Found: c 48.70%, 6.433%, P=12.95%, S=13.14%, C=48".63%-, 'H=6-.56%-. t;

d =1.208 g./cc., 1.1. 3 1. 5.430. LD on rats. orally mg./kg. Spider mites 0.01%, 90% .(ovioidal activity). Black bean aphids 0.01%.,...-70% (systemic action).

Example- .5 v 6C":111t'- 15 G'Hi- I SCaHc 44.5 grams 0.25 mol.) at the sodiumsalt of S-ethyl 'thioresorcin are, disscrrl-vedv in 2.00 ml. of ethyl methyl ketone and at, a temperature. ofabout 351-40 C. there are added- 41 grams of methyl phpsphoniicacid,isopropyl ester chloride. After heating for one hour the reaction mixture is cooled. "Ether is added and this'mixture is washed with water. After drying over sodiurm sulfa-te the solvent isdistilled ofiin vacuot andthe oily residue is distilled further in high vacuo. There are obtained 64 grams of the new ester (B.P. M1 91 C.). Yield: 93% of the theoretical.

d =l.135 g./oc.,. n =1.531=3.

. 30 C 53.10%, H: 6.92%; P 1.10.6170,. C =,53.20,%, H=6.88%. 7

LD on rats orally- 2-5. mgJkg.

Toa sodium methylate, solution containingv 0.2 mol of sodium there is added a solutionof 28 grams ofp-methyl mercapto' phenol in- 100 ml. ofbenzene/ The. methanol is, distilled off while benzene isadded sothatatlastthere is obtained 'a suspension of the sodium salt inbenzene. Atlast the benzene isdistilled oifz invacumandt-he'd'ry sodium phenolate is dissolved in 100 cc. of unhydrous acetone. To this solution there are added at a temperature of 20 C. 34 grams of methyl thionophosphonic acid-O-ethyl ester chloride (B.P. 12 mm./63 C.). After completion of the reaction the mixture isheated for another hour on the steam bath. Thereaction mixturev isv diluted; with benzeneand then washed with Water, a soda solution andonce again with water.v The. benzenic layer is dried over sodium sulfate and thesolize'ntis distilled oif invacuo. There are ohtaified 51 grams of the new ester as a light 'yello'wish oil (B.P'. M1 mm./ 102 C.)

Yield: 99% of the theoretical-.-

.L D onrats orally 2.5 mg/kg. 7 g I Colorado bottles are killed completely with solutions of 0.01%. Black bean aphids and: spider mites are killed with solutions of 0.001%. The compound has a remarkable ovicidal efi'ect against eggs of spider mites.

Example 7 A OCH oHts'Q-O-A r \cn, g

28 grams (0.2- mol) of p-methyl mercaptophenol are transformed to the sodium salt as described in Example 6' and the product isdissolved in 15 01rd.- of acetone. At 75 a temperatur of abort-2? there are added 30'grarns of methyl thionophosph'onic acid-O-methyl ester emanate 61318511 mm./53= C.) The reaction mixture-is heated for another hour on the boilingwater batht- Then-ibis worked up] as described in Example There are-"obe trained 49 grams of the new ester (BKP. m. min/108 Yield: 98% of the theoretical.

LDgs on rats orally-2.5. mg./kg.

Example 8 OHPS OA 471grams} (0.3 mol) of methyl-p hydroxyphenyl sulfoxide are dissolved'in 120ml. of I ethyl methyl ketone and to, this solution there are added 42 grams. of potassium carbonate. After boiling for /2 hour there" are added to this, suspension 48 of methyl phosphoxii'c acid-O- methyl ester chlo'ride' (B.P. 1*.1 mm./53i) at a tem erature of 40-50" C. After" completion of the reaction the mixture is boiled for another hour and then filtered" off from the salts. Thenthe mixture is diluted with 2'50 benzene. This dilution is washed with a soda solution and at last with water. After dryingove'r' sodium sulfate the solvent is distilled (sit invacuo. Thereare obtained 70 grams of the new ester (B'=.P; M1 mm./ 110 C.).

Yield: 88% of the theoretical.

Example 9' S O CHI eraser-Q0 A Example 10 31- grams of p-eth'yl mercapto' phenol are transformed into the sodium salt as described in Example- 6; andthen dissolved in nil. of acetone. To, this solution there are added at a temperature of 30-50 C. 32' grams of methyl" thionophosphonic acid-'O-me'th'yl ester chloride (13.1. 11 mm'./53" C.) and after completion of the reaction the mixture; is heated for another hour on the steam bath. Thenthe mixture is worked up as described in Example 6. There are obtained 52 grams of the new ester, which distils at 0.01 mm- Hg at C. Yield: 98% of the theoretical.

LD on rats orally 5 mgJkg.

Example 11 S OCIHI of methyl thionophosplionic'acid-O-ethyl ester chloride (B.P.lZ mm./63. C.) and after completion of the reaction thetemperature is kept at 100 .C. for another hour. r Thenthe reaction product is worked up as described in Example 6. There are obtained 55 grams of the new ester (B.P. 0.01 mm./l25 C.). Yield: 98% of the theoretical.

LD rats orally mg/kg- Example 12 I S OCHa CH: SCHs 37 grams (0.26 mol) of Z-methyl mercaptophenol are transformed into the sodium salt as described in Example 6 and the sodium salt is dissolved in 120 ml. of acetone. To this solution there are added '42grams of methyl thionophosphonic acid-O-methyl-ester chloride (B.P. 11 min/53 C.). After completion of the reaction the reaction product is boiled for another hour. Then it is worked up as described in Example 6. There are obtained 64.5 grams of the new ester (B.P. 0.01 mm./ 104 C.). -'Yield: 99% of the theoretical.

LD on rats orally 100 mg./ kg.

Example 13 S OCzHs o i' H I CH: S OH:

28 grams (0.2 mol) of 2-methyl mercaptophenol are transfonned into the sodiumsalt as described in Example 6 and the sodium salt is dissolved in 100 cc. of acetone. At a temperature of 40 C. there are added '34 grams of methyl -thionophosphonic .acid-O-ethyl -ester chloride (B.P. 12mm./ 63 C.-). After completion of the reaction the reaction product is boiled for-another hour. After workingup as described in Example 6 there are obtained 52 grams of the new ester-(B.P. 0.01 mm./108 C.). Yield: 98% of the theoretical. V

Example 14 agar I CHa S CH:

31 grams of 2-methy1 mercapto-4-methyl phenol (0.2 mol) are transformed into thesodium salt as described in Example 6. I The sodium chloride is dissolvedin 100 cc. of acetone. At atemperature of 30-50" C. there are added '32 grams of methyl thionophosphonic acid-O- methyl ester chloride. After completion of the reaction the mixture is heated to the boiling point for another hour. After working up as described in Example 6' there are obtained 52 grams of the new ester (B.P. 0.01 mm./ 117 C.). Yield: 98% of the theoretical.

Example 15 I s ojo'm] l' SCH;

25 grams (0.14 mol) of Z-methyl mercapto-4'chloro phenol are transformed into the sodium salt as described in Example 6. The sodium salt is dissolved in 100 ml. of acetone. At a temperature of 45-50? C. there are added" 23 grams ,of methyl thionophosphonic;acid-0'- methylester. chloride (B.P. l1 trim/53). After completionof .the reaction. the reaction mixture, is boiled 8 for another hour. After working up as described in Example 6 there are obtained 39 grams of the new ester (B.P.0.01mm./l'1l', C.). Yield: 99% of the theoreti- 23 grams (0.09 mol). of 2-methyl mercapto-4,6-di-tert. butylphenol are transformed into the sodium salt as described in Example 6. The sodium salt is dissolved in 50 ml. of methyl ethyl ketone. At a temperature of 50- C. there are added 18 grams'of methyl thionophosphonic acid-O-ethyl ester chloride (B.P. 12 mm./ 63 C.). After completion of the reaction the reaction mixture is boiled for another hour. After working up as described in Example 6 there are obtained 28 grams of the new ester (B.P. 0.01 man/122 C.). Yield: 98% of the theoretical. I

' Density: d =1.140, refraction: n =1.5575.

We claim: a a

1. Phosphonic acid esters of the following formula (A), R: in which R and R stand for a member selected from the group consisting of lower alkyl and phenyl radicals, Ar stands for phenyl radicals, R stands for lower alkyl radicals, with 1 to 4 carbon atoms, X stands for a member selected from the group consisting of oxygen and-sulfur,

and n stands for a member selected from the numbers 'of 0, 1 and 2.

2. Phosphonic acid esters of the following formula in which R and R stand for a member's'elected from the groupconsisting of lower alkyl and phenyl radicals, Ar stands for phenyl radicals, R stands for lower alkyl radicals, with 1 to 4 carbon atoms, X stands for a member selected from the group consisting of oxygen and sulfur.

' 4. Phosphonic acid esters of the following formula R%Ar-Oi='-R in which. R and R stand for a member selected from the group consisting of loweralkyl and phenyl radicals, Ar stands for phenyl radicals, R2 stands for'lower alkyl radicals, with 1 to 4 carbon atoms, X stands for a member selected from the group consisting of oxygen and sulfur.

References Cited in the file of this patent UNITED STATES PATENTS 2,503,390 Jelinek Apr. 11, 1950 2,803,580 Metivier Aug. 20, 1957 .j j FOREIGN, PATENTS 814,152, Germany Sept. 20, 1951 

1. A PHOSPHONIC ACID ESTERS OF THE FOLLOWING FORMULA 